PROJECT SUMMARY The proposed project aims to develop and test a novel ultrasound-guided delivery system for implanting transcatheter aortic valves. This new technology will enable accurate positioning and repositioning of the device during implantation to ensure valvular competency, and avoid paravalvular leakage and coronary ostia obstruction. Currently, real-time fluoroscopy imaging is insufficient to accurately identify optimal deployment areas in the aortic anatomy. Improper implantation may result in obstruction of coronary ostia by the implanted valve, or debris dislocation in a highly calcified valve. Transesophageal Echocardiography (TEE) has been investigated as a complementary imaging modality for TAVR procedures; however, TEE operates at a lower resolution, can result in significant complications, and is uncomfortable for most patients. Additionally, TEE requires general anesthesia during the procedure, and a push is being made to perform TAVR solely under conscious sedation, which would not allow the use of TEE over long time periods. This project aims to combine intravascular ultrasound (IVUS), which has been used successfully to optimally position coronary artery stents, with our repositioning/retrievable delivery catheter for TAVR procedure. We hypothesize that IVUS will assist in accurate imaging of the aortic annulus and root, allowing for an improved TAVR implantation procedure compared to conventional TEE-guided procedures. We will accomplish the following specific aims within this award's two-year duration: Specific Aim 1: Design and construct an integrated ultrasound-guided delivery system for accurate positioning/repositioning of transcatheter aortic valves. Specific Aim 2: Demonstrate the clinical feasibility of IVUS-guided valve implantation by delivering the valves in a sheep model (within a previously-implanted calcified polymeric aortic valve) and testing its functionality. Then compare the procedure's outcome variables to commonly-practiced TEE-guided implantation procedures.